The present invention is concerned with an improved antiinflammatory composition and method of treating inflammation which employs non-steroidal antiinflammatory agent such as piroxicam, or a pharmaceutically acceptable salt thereof (particularly the ethanolamine salt of piroxicam) in combination with pyridoxine, a member of the vitamin B.sub.6 complex. The generic names used here and elsewhere herein are from the USAN and the USP Dictionary of Drug Names, 1961-1981, Griffiths et al., ed., U.S. Pharmacopeial Convention Inc., Rockville, MD., 1984, have subsequently been assigned and published as official USAN names, and/or appear in The Merck Index 10th Edition.
Gastrointestinal irritation, including ulcers, is a side effect commonly associated, to one degree or another, with antiinflammatory agents. In many cases, individuals requiring such antiinflammatory treatment are precluded from enjoying the benefits thereof because of their susceptibility to such side effects. The present combination of a non-steroidal antiinflammatory agent with pyridoxine permits desirable antiinflammatory therapy while preventing or ameliorating said gastrointestinal irritation or ulcers.
There are no known reports bearing on the use of pyridoxine to reduce gastric side effects of non-stereoidal antiinflammatory agent. However, pyridoxine (1.1 mg/kg, injection) has been reported by Lindenbaum et al., Nutr. Metabol. 17, 368 (1974), to reduce the frequency of ulcers in the restrained mouse ulcer model. Pyridoxine by subcutaneous injection has been reported to alleviate the pain, but not promote the healing, of gastric ulcers [Lemeshko et al., Sov. Med. 29, 33 (1966)]; and in combination with anabolic hormones to produce a better antirelapse effect in patients with chronic gastritis, but not in patients with peptic ulcers [Dovgyallo et al., Klin. Med. (Mosk) 51, 57 (1973)]. Schumacher et al., Am. J. Clin. Nutr. 28, 1200 (1975) reported that patients with rheumatoid arthritis had lower than normal plasma levels of pyridoxal phosphate. Treatment of these patients with pyridoxine hydrochloride (50-150 mg/day) for 3 months resulted in increases (2-5 fold) in plasma levels of pyridoxal phosphate. However, no clinical improvements in the disease were noted. Even though most patients in this study were taking aspirin (and in many cases one or two additional agents) no comments were made on the side effect profile observed with this therapy (pyridoxine plus aspirin). In later studies it has been concluded that reduced levels of plasma levels of vitamin B.sub.6 in patients suffering ulcer disease results from the antiulcer diet of the patient; although the duration of the disease was not dependent on B.sub.6 levels, duration of exacerbation of the disease was dependent upon B.sub.6 levels as one of several factors (Litinskaya, Vrach. Delo. 1977, 93).
Various combinations of vitamins B.sub.1, B.sub.6 and B.sub.12, particularly in injectable form, have been indicated for use in various neuropathic disorders, such as neuritis and neuralgia (see the German "Rote Liste 1981", abstracts 05-439 to 05-447). Based on this rationale, clinicians have sought to influence nerve metabolism by the addition of these neurotropic vitamins to analgesic and/or antiinflammatory combinations in an effort to control the neuralgic symptoms frequently in rheumatic disease [for example, see Gerhold, Fortsch. Therapy, 92 (supplement), pp. 1-4 (1974) concerning a combination of phenylbutazone, ampyrone (aminophenazone), vitamins B.sub.1, B.sub.6 and B.sub.12, and escin; see also Rote Liste 1981 abstracts 05-228 to 236, 05-267 to 284; 05-336; 05-407 to 430]. There is no prior evidence that such combinations improve the tolerance of antiinflammatory agents. Indeed in a typical, short-term clinical study with flufenamic acid in combination with vitamins B.sub.1, R.sub.6 and B.sub.12, 5 of 26 patients were withdrawn from the study for lack of toleration [Pietrogrande et al., Clin. Ter. 71, pp. 531-537 (1974)].